As reported on Tech Times, Sanofi has reported positive results from its Phase 3 Baby-COMET study evaluating Nexviazyme (avalglucosidase alfa) in infants with infantile-onset Pompe disease (IOPD), one of the most severe and rapidly progressive forms of the rare genetic disorder. According to the company, the trial met all primary and secondary endpoints, with no serious treatment-related adverse events observed. Sanofi plans to submit a supplemental application to the U.S. Food and Drug Administration (FDA) in the second half of 2026 seeking approval for use in infants younger than six months.
If approved, the expanded indication would provide clinicians with a therapy supported by Phase 3 data specifically in newborns and young infants identified through modern newborn screening programs.
A Critical Disease Requiring Early Intervention
Pompe disease, also known as glycogen storage disease type II, is a rare inherited lysosomal storage disorder caused by deficiency of the enzyme acid alpha-glucosidase (GAA). Without adequate GAA activity, glycogen accumulates within cells, progressively damaging muscle tissue throughout the body.
The infantile-onset form is particularly aggressive. Symptoms often emerge within the first weeks of life and can include profound muscle weakness, feeding difficulties, respiratory problems, and enlargement of the heart. Without treatment, many affected infants experience life-threatening cardiorespiratory complications during their first year.
The widespread adoption of newborn screening for Pompe disease in the United States has enabled earlier diagnosis, making effective treatment during the neonatal period increasingly important.
Engineering a More Efficient Enzyme Replacement Therapy
Nexviazyme is an enzyme replacement therapy (ERT) designed to improve delivery of replacement GAA to affected tissues. Like other ERTs used for lysosomal storage disorders, it relies on mannose-6-phosphate (M6P) receptors to transport the infused enzyme into cells and ultimately into lysosomes, where glycogen breakdown occurs.
Sanofi developed avalglucosidase alfa to enhance this targeting process. Compared with first-generation alglucosidase alfa products, Nexviazyme contains substantially higher levels of M6P structures, which may improve uptake into skeletal and cardiac muscle. The therapy received FDA approval in 2021 for patients with late-onset Pompe disease aged one year and older and has broader approvals in several international markets.
Baby-COMET Study Meets All Endpoints
The Baby-COMET trial was designed to evaluate Nexviazyme in treatment-naive infants aged 12 months or younger diagnosed with IOPD. The international, multicenter study enrolled 17 participants, all of whom received intravenous avalglucosidase alfa at a dose of 40 mg/kg every other week.
The primary endpoint assessed the proportion of infants aged six months or younger who remained alive and free from invasive ventilation after 52 weeks of treatment.
According to Sanofi, the study achieved its primary objective and also met all secondary endpoints. Investigators reported positive findings across multiple clinically meaningful measures, including:
- Survival without invasive ventilation at 12 and 18 months of age
- Improvements in cardiac structure, measured by left ventricular mass Z-scores
- Gains in motor function based on the Alberta Infant Motor Scale
- Reductions in urinary glucose tetrasaccharide, a biomarker associated with glycogen accumulation
Because IOPD is a rare and often fatal disease, Baby-COMET used a single-arm design rather than a randomized control group. This approach is commonly accepted in severe pediatric rare diseases where withholding treatment would present ethical concerns.
Favorable Safety Findings
The safety profile reported in Baby-COMET was consistent with previous experience using Nexviazyme.
Researchers observed:
- No treatment-related serious adverse events
- No deaths during the study
- No discontinuations linked to treatment
- Infusion-related reactions in approximately 29% of participants, all considered manageable
Additional details regarding immunogenicity, including outcomes in CRIM-negative patients who may be at greater risk for immune responses against replacement enzymes, are expected in future presentations of the data.
Regulatory Plans and Clinical Implications
Sanofi intends to seek a U.S. label expansion later in 2026. Approval would broaden access to Nexviazyme for infants diagnosed during the earliest months of life, a period when treatment can have the greatest impact on survival and disease progression.
The complete Baby-COMET dataset is scheduled for presentation at the 19th International Congress on Neuromuscular Diseases in Florence, Italy, where investigators are expected to provide detailed efficacy and safety results.
For clinicians treating Pompe disease, the study may offer important evidence supporting the use of enhanced enzyme replacement therapy shortly after diagnosis through newborn screening.
Broader Relevance for Lysosomal Storage Disorders
Beyond Pompe disease, the findings may have implications for the wider field of lysosomal storage disorders. Many enzyme replacement therapies depend on the same M6P receptor pathway to deliver treatment into cells, and insufficient tissue uptake remains a challenge across several rare diseases.
The positive Baby-COMET results suggest that improving receptor targeting through enhanced M6P content could be a viable strategy for next-generation ERT development. However, important limitations remain. Intravenous enzyme therapies do not cross the blood-brain barrier, leaving neurological manifestations beyond the reach of current treatment approaches.
As gene therapies and other advanced modalities continue to evolve, Nexviazyme’s latest clinical results represent a significant step forward for infants with Pompe disease while highlighting both the progress and remaining challenges in managing lysosomal storage disorders.
